摘要
目的探讨半乳糖凝集素-3(Gal-3)诱导血管平滑肌细胞增殖及促进大鼠动静脉内瘘(AVF)狭窄发生的作用,并探讨可能机制。方法取30只AVF大鼠,随机数字法分为AVF组、柑橘果胶组、联合组,每组10只;另取10只大鼠行假手术,设为假手术组。联合组灌胃柑橘果胶生理盐水溶液(含柑橘果胶0.15 mg/kg),尾静脉注射表皮生长因子[细胞外信号调节激酶(ERK)通路激动剂(EGF)](10μg/kg);柑桔果胶组灌胃柑橘果胶生理盐水溶液(0.15 mg/kg),尾静脉注射等体积PBS;假手术组、AVF组灌胃等量生理盐水,尾静脉注射等体积PBS。每日1次。干预4周。MTT法检测血管平滑肌细胞增殖能力;ELISA法检测血清炎症因子[肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)]水平;ELISA法检测血管组织转化生长因子-β1(TGF-β1)、血管内皮细胞生长因子(VEGF)水平;Western blot法检测血管组织p38丝裂原活化蛋白激酶(MAPK)、p-p38 MAPK、ERK1/2、p-ERK1/2蛋白表达量。结果与AVF组比较,柑橘果胶组24、48、72 h吸光度值,血清TNF-α、IL-6水平,血管组织TGF-β1、VEGF水平,p-p38 MAPK/p38 MAPK、p-ERK1/2/ERK1/2降低(P<0.05);与柑橘果胶组比较,联合组24、48、72 h吸光度值,血清TNF-α、IL-6水平,血管组织TGF-β1、VEGF水平,p-p38 MAPK/p38 MAPK、p-ERK1/2/ERK1/2升高(P<0.05)。结论Gal-3抑制剂改良柑橘果胶可抑制血管平滑肌细胞增殖及炎症反应,缓解AVF狭窄,并抑制ERK信号通路活性。
Objective To explore the effect of Galectin-3(Gal-3)on the proliferation of vascular smooth muscle cells and the stenosis of arteriovenous fistula(AVF)in rats and explore the possible mechanism.Methods Thirty AVF rats were selected and randomly divided into AVF group,citrus pectin group and combination group,10 in each group.Another 10 rats were sham-operated and set as the sham-operated group.The combination group was given citrus pectin(0.15 mg/kg)by gavage,and epidermal growth factor[extracellular signal-regulated kinase(ERK)pathway agonist(EGF)](10μg/kg)was injected into the tail vein.In the citrus pectin group,citrus pectin(0.15 mg/kg)was administered by gavage,and an equal volume of PBS was injected into the tail vein.The sham operation group and the AVF group were given the same volume of normal saline,and the same volume of PBS was injected into the tail vein.One time a day.Intervention for 4 weeks.The proliferation ability of vascular smooth muscle cells was detected by MTT method.The levels of serum inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected.The levels of vascular tissue transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)were detected.Western blot was used to detect the protein expressions of p38 mitogen-activated protein kinase(MAPK),p-p38 MAPK,ERK1/2 and p-ERK1/2 in vascular tissue.Results Compared with the AVF group,the absorbance values at 24,48,and 72 h,serum TNF-α,IL-6 levels,vascular tissue TGF-β1,VEGF levels,p-p38 MAPK/p38 MAPK,p-ERK1/2/ERK1/2 were decreased in the citrus pectin group(P<0.05).Compared with the citrus pectin group,the absorbance values at 24,48,and 72 h,serum TNF-α,IL-6 levels,vascular tissue TGF-β1,VEGF levels,p-p38 MAPK/p38 MAPK,p-ERK1/2/ERK1/2 were increased in the combined group(P<0.05).Conclusion Gal-3 inhibitor modified citrus pectin can inhibit the proliferation and inflammatory response of vascular smooth muscle cells,and relieve AVF stenosis,and inhibit the activity of ERK signaling pathw
作者
孙利军
阮琳
赵文婷
任广伟
SUN Lijun;RUAN Lin;ZHAO Wenting;REN Guangwei(Department of Nephrology,The First Hospital of Hebei Medical University,Shijiazhuang 050031,China)
出处
《西部医学》
2023年第3期331-335,340,共6页
Medical Journal of West China
基金
河北省重点研发计划项目(21377747D)。
